小鼠外侧膝状体双眼神经元的关键期可塑性

For a long period, it is generally accepted that layer 4 of visual cortex are the first place that visual information from both eyes integrate following the retina-LGN-V1 pathway. In this case, no critical period for ocular dominance plasticity is believed to exist in the LGN. However, recently with both in vivo electrophysiology and single-cell transsynaptic tracing, it is found that there are binocular neurons in mouse LGN receiving inputs from both eyes, and some forms of ocular dominance plasticity do exist in the LGN. However, there is possibility that the binocular-responsive neurons actually receive binocular inputs from other parts of the visual system, not directly from retina. On the other hand, whether the LGN has a critical period, just like visual cortex, is unknown. To figure out these questions, applicant will use both anatomical tracing and functional studies to investigate the number and functions of binocular neurons in mouse LGN. A developmental study will be performed to find out the exact time window of the critical period in the LGN. Applicant will also use the DREADD (designer receptors exclusively activated by designer drugs) approach to specifically silence the LGN binocular neurons to see the effects on cortical critical period. These experiments would broaden our knowledge of the development of visual circuits and provide new approaches on the treatment of visual disorders such as amblyopia.

长期以来，普遍认为视觉皮层的4层是双眼视觉信息沿视网膜-丘脑-视皮层通路的第一次整合。因此，外侧膝状体被认为是不存在眼优势可塑性的关键期的。然而，最近在体电生理及单细胞跨突触追踪的实验结果发现小鼠丘脑存在接收来自双眼输入的双眼神经元。另外，类似眼优势可塑性的现象最近也在外侧膝状体上被发现。然而，存在这样的可能性，双眼神经元实际上是从视觉系统的其他部分接收到双眼输入，而不是直接来自视网膜。另一方面，丘脑是否存在一个像视觉皮层的关键期还是未知的。为了弄清楚这些问题，申请人将使用解剖学与功能学的方法研究小鼠外侧膝状体双眼神经元的数量和功能，同时将使用发育学的方法找出丘脑关键期的确切时间窗。申请人也会使用化学遗传学方法DREADD特异性沉默丘脑双眼神经元，以此观察它对皮层关键期的作用。这些实验将扩大我们对视觉回路发育的认识，并为弱视等视觉疾病的治疗提供新的思路。

在初级视觉皮层中，眼优势可塑性的关键期是重要的早期发育阶段，可以根据视觉经验塑造神经环路的成熟。最近的研究表明，在小鼠背外侧膝状体（dLGN）中存在类似视觉皮层的眼优势可塑性。目前还不清楚其确切的时间窗口，以及促进dLGN的眼优势可塑性形成的神经环路机制。利用在体电生理学，我们确定了从睁眼到青春期的dLGN的眼优势可塑性的关键期。在dLGN双眼神经元中，还存在着一个从对侧优势到双眼均势的眼优势形成过程。用蝇蕈醇瞬间失活视觉皮层对dLGN眼优势偏向或可塑性没有影响。用N-甲基-d-天门冬氨酸短期失活视觉皮层可以逆转均势的眼优势偏向的形成，而长期失活视觉皮层可以将dLGN的发育维持在一个不成熟的阶段。我们的结论是，dLGN眼优势偏向和可塑性存在两个不同的发育过程，视觉皮层的反馈输入在dLGN关键期中对它们起着不同的作用。这个结果为弱视的治疗提供了新的思路。